FIGURE 3-36 Determination of polyubiquitin function by the lysine used for inter-ubiquitin isopeptide bonds. Different ubiquitin ligases catalyze polyubiquitinylation of distinct target (substrate) proteins (colored ovals) using distinct lysine side chains of ubiquitin molecules (purple) to generate the inter-ubiquitin isopeptide linkages (blue) with Gly-76 of the adjacent ubiquitin. Dotted blue arrows represent additional ubiquitins in the chain that are not shown. The lysine used for the isopeptide bonds determines the function of the polyubiquitinylation. For example, polyubiquitins with Lys-48:Gly-76 isopeptide bonds direct the target to proteasomes for degradation. Those that use Lys-63, Lys-33, and Lys-11 influence signaling, T-lymphocyte control, and cell division, respectively. Isopeptide bonds involving ubiquitin’s Lys-6, Lys-27, and Lys-29 and bonds using its N-terminal amino group (not shown) can also be used to generate polyubiquitin chains.